title: Sub-optimal CD4 reconstitution despite viral suppression in an urban cohort on antiretroviral therapy (ART) in sub-Saharan Africa: frequency and clinical significance.
abstract: BACKGROUND
  A proportion of individuals who start antiretroviral therapy (ART) fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV research cohort in Kampala, Uganda.
  
  
  METHODS
  We analyzed data from a prospective research cohort of 559 patients initiating ART between 04/04-04/05. We described the patterns of SO-CD4 both in terms of:- I) magnitude of CD4 cell increase (a CD4 count increase < 50 CD4 cells/microl at 6 months, <100 cells/microl at 12 months; and <200 cells/microl at 24 months of ART) and II) failure to achieve a CD4 cell count above 200 cells/microl at 6,12 and 24 months of ART. Using criteria I) we used logistic regression to determine the predictors of SO-CD4. We compared the cumulative risk of clinical events (death and/or recurrent or new AIDS-defining illnesses) among patients with and without SO-CD4.
  
  
  RESULTS
  Of 559 patients initiating ART, 386 (69%) were female. Median (IQR) age and baseline CD4 counts were 38 yrs (33-44) and 98 cells/microl (21-163) respectively; 414 (74%) started a d4T-based regimen (D4T+3TC+NVP) and 145 (26%) a ZDV-based regimen (ZDV+3TC+EFV). After 6, 12 and 24 months of ART, 380 (68%), 339 (61%) and 309 (55%) had attained and sustained HIV-RNA viral suppression. Of these, 78 (21%), 151 (45%) and 166 (54%) respectively had SO-CD4 based on criteria I), and 165(43%), 143(42%) and 58(19%) respectively based on criteria II). With both criteria combined, 56 (15%) and 129 (38%) had SO-CD4 at 6 and 12 months respectively. A high proportion (82% and 58%) of those that had SO-CD4 at 6 months (using criteria I) maintained SO-CD4 at 12 and 24 months respectively. There were no statistically significant differences in the incidence of clinical events among patients with [19/100PYO (12-29)] and without SO-CD4 [23/100PYO (19-28)].
  
  
  CONCLUSIONS
  Using criteria I), the frequency of SO-CD4 was 21% at 6 months. Majority of patients with SO-CD4 at 6 months maintained SO-CD4 up to 2 years. We recommend studies of CD4 T-cell functional recovery among patients with SO-CD4.
authors.affiliation: Infectious Diseases Institute, Facluty of Medicine, Makerere University Kampala, Uganda. drdamalie@yahoo.com
authors.forename: Damalie
authors.initials: D
authors.lastname: Nakanjako
authors.forename: Agnes
authors.initials: A
authors.lastname: Kiragga
authors.forename: Fowzia
authors.initials: F
authors.lastname: Ibrahim
authors.forename: Barbara
authors.initials: B
authors.lastname: Castelnuovo
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Easterbrook